Shelley Darlington (Anna Faris) is a Playboy Bunny living the life of luxury. The day after her twenty-seventh birthday, she awakes to find a note from Hugh Hefner asking her to pack up and leave. Saddened, she hits the road looking for a new life, and she happens to see girls who remind her of herself: beautiful and fun. She immediately follows them and sees that they live in luxury ,too. She tells them her situation and asks to join, not knowing that they are in a sorority, and is rejected because she is not a student -- and because the fact that the girls are completely stuck up. She sees there are ladies that watch over the girls and live there also; but, after asking to join them, she is rejected again.
Shelley then finds another sorority, Zeta Alpha Zeta, whose members are socially awkward and reject her, too: all except Natalie (Emma Stone), a bespectled virgin who tries her best to lead the Zetas. And once the Zetas see that Shelley is able to attract boys and friends, their antipathy changes. She turns the girls around and teaches them everything they need to know to surpass the other girls. During this process, she meets Oliver (Colin Hanks), and although she can teach everyone else how to flirt, she has to get help from her new "students" in order to interact with him successfully.
As the girls of Shelley's sorority become more popular on campus, they realize that they have changed themselves too much to please other people -- and they blame Shelley for that. Just then, the Playboy Mansion calls Shelley to tell her that she was set up and that they never wanted her to leave. It would seem perfect for her to go back to her old life; but when she tries, she sees she cares far too much for her girls, who have come to care for her as well. Shelley decides to fix the devastation that the Phi Iota Mus have wrecked upon the Zeta Alpha Zetas while she was gone, and, with help from everyone, she succeeds. The Zetas, who have decided to try to be a cross between themselves and Shelley's suggestions, also play matchmaker, and manage to fix Shelley up with Oliver.